To illustrate the improved risk prediction performance in real data, we applied AnnoPred to five human complex diseases—Crohn’s disease (CD), breast cancer (BC), rheumatoid arthritis (RA), type-II diabetes (T2D), and celiac disease (CEL). We first estimated GWAS signal enrichment in different annotation categories (Methods). Enrichment pattern varies greatly across diseases (Fig 2A; S1 Table), reflecting the genetic basis of these complex phenotypes. Functional genome predicted by GenoCanyon was consistently and significantly enriched for all five diseases. Blood was strongly enriched for three immune diseases, namely CD (P = 8.9×10−12), CEL (P = 7.0×10−15), and RA (P = 9.9×10−6), while gastrointestinal (GI) tract was enriched in CD (P = 2.6×10−5) and CEL (P = 1.4×10−4), both of which have a known GI component. For BC, epithelium (P = 7.4×10−4), GI (P = 5.9×10−3), and muscle (P = 6.1×10−3) were significantly enriched. A few studies have shown that breast cancer could arise from epithelial cells [19, 20]. The connections between breast cancer and muscle as well as GI tract have also been previously suggested [21, 22]. In addition, studies have suggested that
